MicroRNA-125b down-regulation mediates endometrial cancer invasion by targeting ERBB2.
Summary of "MicroRNA-125b down-regulation mediates endometrial cancer invasion by targeting ERBB2."
Background: MicroRNAs (miRNAs) are small non-coding nucleotides that regulate mRNA stability and protein expression by imperfect base pairing with the 3'-untranslated region (3'UTR) of target mRNAs. Many miRNAs have been documented to be aberrantly expressed in human cancers, but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. The objective of this study was to investigate the effect of miR-125b on EEC development and to explore its molecular mechanism in EEC carcinogenesis. Material/Methods: Real-time quantitative PCR was applied to evaluate the expression level of miRNA-125b in EEC and normal endometrium (NE) samples. The invasion ability of miR-125b in EEC HEC1B cells was analyzed by Transwell assay after pre-miR-125b or anti-miR-125b transfection. For the invasion mechanism analysis of miR-125b on HEC1B cells, miRBase, TargetScan, miRanda and PicTar were used to predict the possible target gene of miR-125b. Luciferase activities assay, cotransfection and Western blot were used to reveal that the predicted target genes of miR-125b were direct and specific. RNA interference technology was used to confirm that the invasion inhibition of miR-125b was directly induced by ERBB2. Results: Our study showed that miR-125b was down-regulated in human EEC specimens compared to that in NC specimens. Over-expression of miR-125b in HEC1B cells inhibited EEC invasion and this inhibitory effect on HEC1B cells could be restored by miR-125b knock down. Mechanism analysis revealed that ERBB2 was a direct and specific target of miR-125b. The inhibitory effect on EEC cell invasion was mediated by miR-125b inhibition of the translation of a proto-oncogene, ERBB2. Conclusions: Aberrantly expressed miR-125b contributes to HEC1B cells invasion partly through directly down-regulating ERBB2 protein expression in EEC. This miRNA signature offers a novel potential therapeutic strategy for EEC.
Affiliation
Department of Neurobiology, China Medical University, Shenyang, P.R. China and Institute of Pathology and Pathophysiology, China Medical University, Shenyang, P.R. China.
Journal Details
This article was published in the following journal.
Name: Medical science monitor : international medical journal of experimental and clinical research
ISSN: 1643-3750
Pages: BR149-155
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22460089
- DOI: http://dx.doi.org/
Medical and Biotech [MESH] Definitions
Endometrial Stromal Tumors
Neoplasms of the endometrial stroma that sometimes involve the MYOMETRIUM. These tumors contain cells that may closely or remotely resemble the normal stromal cells. Endometrial stromal neoplasms are divided into three categories: (1) benign stromal nodules; (2) low-grade stromal sarcoma, or endolymphatic stromal myosis; and (3) malignant endometrial stromal sarcoma (SARCOMA, ENDOMETRIAL STROMAL).
Hamartoma Syndrome, Multiple
A hereditary disease characterized by multiple ectodermal, mesodermal, and endodermal nevoid and neoplastic anomalies. Facial trichilemmomas and papillomatous papules of the oral mucosa are the most characteristic lesions. Individuals with this syndrome have a high risk of BREAST CANCER; THYROID CANCER; and ENDOMETRIAL CANCER. This syndrome is associated with mutations in the gene for PTEN PHOSPHATASE.
Endometrial Neoplasms
Tumors or cancer of ENDOMETRIUM, the mucous lining of the UTERUS. These neoplasms can be benign or malignant. Their classification and grading are based on the various cell types and the percent of undifferentiated cells.
Endometrial Hyperplasia
Benign proliferation of the ENDOMETRIUM in the UTERUS. Endometrial hyperplasia is classified by its cytology and glandular tissue. There are simple, complex (adenomatous without atypia), and atypical hyperplasia representing also the ascending risk of becoming malignant.
Sarcoma, Endometrial Stromal
A highly malignant subset of neoplasms arising from the endometrial stroma. Tumors in this group infiltrate the stroma with a wide range of atypia cells and numerous mitoses. They are capable of widespread metastases (NEOPLASM METASTASIS).
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